During World War II the station was used heavily by military troops. After the war though, the decline in railway travel began as more and more people would use cars for vacation or other travel. Service to the station was cut back and several unsuccessful attempts to sell the building were made in the 1950's and 1960's. By then, the station's restaurant and several shops were closed, as was the biggest part of the waiting room, and only 2 ticket windows would serve passengers.

When Amtrak took over the station in 1971 there were attempts to restore MCS to its old glory. The main waiting room and and entrance were reopened and a $1.25 million renovation project started in 1978. Six years later though the building was sold to a transportation company which decided to shut it down. The last Amtrak train departed from Michigan Central Station on January 6, 1988, 74 years and 2 days after the station opened.

During the last 3 decades there has been a lot of discussion about the station's future. Many potential uses have been proposed, among them the redevelopment of the station into a trade processing center, a convention center and casino, or Detroit Police headquarters. In 2009 Detroit City Council asked for the demolition of MCS even though the station has been added to the National Register of Historic Places.

Starting in 2009 works to renovate the station have started by the building's owners. Among them, the removal of asbestos, internal demolition work, removal of water, broken glass and other debris, electricity restoration, and installation of a freight elevator. In 2015, works for the installation of more than 1,000 windows in the building's exterior began. However, there is still no set plan for a future use of the station.

Meanwhile, Michigan Central Station has been featured in films such as Transformers, The Island, Naqoyqatsi and Four Brothers as well as Eminem's music videos. Photographers and urban explorers have been visiting the station for years, making it an iconic example of ruins photography.